Anticipatory reward signals in ventral striatal neurons of behaving rats

It has been proposed that the striatum plays a crucial role in learning to select appropriate actions, optimizing rewards according to the principles of 'Actor-Critic' models of trial-and-error learning. The ventral striatum (VS), as Critic, would employ a temporal difference (TD) learning algorithm to predict rewards and drive dopaminergic neurons. This study examined this model's adequacy for VS responses to multiple rewards in rats. The respective arms of a plus-maze provided rewards of varying magnitudes; multiple rewards were provided at 1-s intervals while the rat stood still. Neurons discharged phasically prior to each reward, during both initial approach and immobile waiting, demonstrating that this signal is predictive and not simply motor-related. In different neurons, responses could be greater for early, middle or late droplets in the sequence. Strikingly, this activity often reappeared after the final reward, as if in anticipation of yet another. In contrast, previous TD learning models show decremental reward-prediction profiles during reward consumption due to a temporal-order signal introduced to reproduce accurate timing in dopaminergic reward-prediction error signals. To resolve this inconsistency in a biologically plausible manner, we adapted the TD learning model such that input information is nonhomogeneously distributed among different neurons. By suppressing reward temporal-order signals and varying richness of spatial and visual input information, the model reproduced the experimental data. This validates the feasibility of a TD-learning architecture where different groups of neurons participate in solving the task based on varied input information.     

Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

OBJECTIVE: Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic changes during regional ischemia in hearts from pigs fed a diet rich in fish oil. METHODS: Pigs received diets rich in fish oil, in sunflower oil, or a control diet for 8 weeks. Hearts were isolated and perfused. Ischemia was created by occluding the left anterior descending artery. Diastolic stimulation threshold, refractory period, conduction velocity, activation recovery intervals and the maximum downstroke velocity of 176 electrograms were measured in the ischemic zone. Spontaneous arrhythmias during 75 min of regional ischemia were counted. RESULTS: More episodes of spontaneous ischemia-induced sustained ventricular tachycardia and ventricular fibrillation occurred in the fish oil and sunflower oil group than in the control group. More inexcitable myocardium was present in the ischemic zone in the group fed fish oil or sunflower oil than in the control group after 20 min of ischemia. After 40 min of ischemia, more block occurred in the control group than in the other groups. The downstroke velocity of the electrograms in the ischemic border zone was lower in the fish oil group and sunflower oil group than in the control after 20 min. CONCLUSIONS: A diet rich in fish oil results in proarrhythmia compared to a control diet during regional ischemia in pigs. Myocardial excitability is reduced in the fish oil and sunflower oil group during the early phase of arrhythmogenesis. In the late phase of arrhythmogenesis, excitability is more reduced in the control group than in the fish oil and sunflower oil group.     

Impact of quality circles for improvement of asthma care: results of a randomized controlled trial

Rationale and aims Quality circles (QCs) are well established as a means of aiding doctors. New quality improvement strategies include benchmarking activities. The aim of this paper was to evaluate the efficacy of QCs for asthma care working either with general feedback or with an open benchmark. Methods Twelve QCs, involving 96 general practitioners, were organized in a randomized controlled trial. Six worked with traditional anonymous feedback and six with an open benchmark; both had guided discussion from a trained moderator. Forty‐three primary care practices agreed to give out questionnaires to patients to evaluate the efficacy of QCs. Results A total of 256 patients participated in the survey, of whom 185 (72.3%) responded to the follow‐up 1 year later. Use of inhaled steroids at baseline was high (69%) and self‐management low (asthma education 27%, individual emergency plan 8%, and peak flow meter at home 21%). Guideline adherence in drug treatment increased (P = 0.19), and asthma steps improved (P = 0.02). Delivery of individual emergency plans increased (P = 0.008), and unscheduled emergency visits decreased (P = 0.064). There was no change in asthma education and peak flow meter usage. High medication guideline adherence was associated with reduced emergency visits (OR 0.24; 95% CI 0.07–0.89). Use of theophylline was associated with hospitalization (OR 7.1; 95% CI 1.5–34.3) and emergency visits (OR 4.9; 95% CI 1.6–14.7). There was no difference between traditional and benchmarking QCs. Conclusions Quality circles working with individualized feedback are effective at improving asthma care. The trial may have been underpowered to detect specific benchmarking effects. Further research is necessary to evaluate strategies for improving the self‐management of asthma patients.     

A pseudo-iatrogenic case of medial clavicular fracture

Medial fractures are the least common type of clavicular fracture (2-10%). The patient is a 29-year-old gynaecology resident with hyper-laxity and sternoclavicular instability. The latter had been surgically stabilized with Dacron((R)) tape, which eroded the bone causing an usura. Acute right shoulder pain occurred 10 years later. CT revealed medial clavicular stress fracture. After 4 weeks of conservative management, internal fixation followed. Five months postoperatively the patient performed all activities without pain. In this patient the weakened medial clavicle due to usura clearly played a role in both the site and nature of the fracture. Furthermore, CT is essential in arriving at the correct diagnosis.     

Nonlinear intravascular ultrasound contrast imaging

Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is investigated using a prototype IVUS system and an experimental small bubble contrast agent. The IVUS system employed a mechanically scanned single element transducer and was operated at a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). Characterization experiments were performed with agent and tissue phantom signals acquired during transducer rotation. The suppression of transmit frequency tissue signals was achieved using a combination of pulse-inversion and bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals suppressed to near the noise floor. Coronary phantom experiments demonstrated the detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel in which the IVUS catheter was situated. These results suggest the feasibility of harmonic IVUS contrast imaging, which may have applications in coronary lumen boundary detection and vasa vasorum imaging.     

Effects of fusion-bone stiffness on the mechanical behavior of the lumbar spine after vertebral body replacement

BACKGROUND: Implants for vertebral body replacement are often inserted together with an additional stabilizing implant, e.g. an internal fixation device. During implantation bone grafts or milled bone is normally added to the anterior implant. Little is known about the stiffening effect of this fusion-bone mass on the mechanical behavior of the corresponding bone region, including the load distribution between the different parts. METHODS: A three-dimensional finite element model of the lumbar spine was created with a vertebral body replacement at L3, a paired internal fixation device between L2 and L4, and left anterolateral fusion bone. The elastic modulus of fusion bone was varied in discrete steps between 0 MPa and 10,000 MPa. The model was loaded to simulate standing, 20 degrees flexion, 15 degrees extension and 6 degrees axial rotation in the lumbar spine. FINDINGS: The elastic modulus of fusion bone has a considerable effect on the compressive force on vertebral body replacement and fusion bone for all loading cases studied. For extension, it also affects intersegmental rotation, the force in the erector spinae muscle, the compressive force on the internal fixator and intradiscal pressure in the adjacent discs. The elastic modulus most strongly affects the different parameters at values between 0 MPa and 500 MPa. INTERPRETATION: Adding bone mass during vertebral body replacement reduces the loads on the ventral implant for all loading cases studied but extension when the fusion-bone stiffens. This protects the implant from fatigue. The load on the fusion bone increases with increasing elastic modulus. Thus bone grafts should be used whenever possible.     

Chronic inhibition of Na+/H+-exchanger attenuates cardiac hypertrophy and prevents cellular remodeling in heart failure

OBJECTIVE: In patients with heart disease, the transition from compensatory hypertrophy to heart failure (HF) is associated with altered calcium handling. Up-regulated Na(+)/H(+)-exchanger (NHE-1) activity underlies increased [Na(+)](i) and disturbance of cellular calcium handling in HF. We hypothesize that chronic inhibition of NHE-1 activity prevents the hypertrophic response, cellular remodeling, and development of HF. METHODS: Rabbits received a control or cariporide (inhibitor of NHE-1) diet for 3 months, starting after induction of combined volume and pressure overload. Age-matched animals served as control. Development of HF was examined echocardiographically and electrocardiographically after 3 months. [Na(+)](i), [Ca(2+)](i), pH(i), and action potentials were measured in left ventricular midmural myocytes with SBFI, indo-1, SNARF, and di-4-anepps. Sarcoplasmic reticulum calcium content was calculated from the response of [Ca(2+)](i) to rapid cooling. Calcium after-transients were elicited by cessation of rapid stimulation (3 Hz) in the presence of 100 nmol/l noradrenalin. RESULTS: Chronic treatment of rabbits with the specific Na(+)/H(+)-exchanger activity inhibitor cariporide greatly attenuated development of hypertrophy and entirely abolished development of HF; the heart/body weight ratio increased only little, no change in lung weight occurred, left ventricular dimensions and fractional shortening changed mildly, ascites was not present, QT duration did not increase, and sudden death did not occur. Chronic cariporide treatment also prevented cellular electrical and ionic remodeling. Myocyte dimensions were unaltered, action potentials were not prolonged, cytoplasmic sodium and NHE-1 activity did not increase, cytoplasmic and SR calcium handling remained undisturbed, and no increase of the incidence of calcium after-transient dependent delayed after depolarizations (DADs) occurred. CONCLUSION: We conclude that enhanced activity of NHE-1 underlies cardiac cellular electrical and ionic remodeling in experimental heart failure, and that chronic dietary treatment with cariporide attenuates hypertrophy, development of HF, and cellular remodeling.     

Low-Amplitude Non-linear Volume Vibrations of Single Microbubbles Measured with an “Acoustical Camera”

Contrast-enhanced ultrasound imaging is based on the detection of non-linear vibrational responses of a contrast agent after its intravenous administration. Improving contrast-enhanced images requires an accurate understanding of the vibrational response to ultrasound of the lipid-coated gas microbubbles that constitute most ultrasound contrast agents. Variations in the volume of microbubbles provide the most efficient radiation of ultrasound and, therefore, are the most important bubble vibrations for medical diagnostic ultrasound imaging. We developed an “acoustical camera” that measures the dynamic volume change of individual microbubbles when excited by a pressure wave. In the work described here, the technique was applied to the characterization of low-amplitude non-linear behaviors of BR14 microbubbles (Bracco Research, Geneva, Switzerland). The amplitude dependence of the resonance frequency and the damping, the prevalence of efficient subharmonic and ultraharmonic vibrations and the amplitude dependence of the response at the fundamental frequency and at the second harmonic frequency were investigated. Because of the large number of measurements, we provide a statistical characterization of the low-amplitude non-linear properties of the contrast agent.     

Biomechanical behavior of MRI-signal-inducing bone cements after vertebroplasty in osteoporotic vertebral bodies: An experimental cadaver study

Background

Conventional water-free polymethylmethacrylate cements are not MRI visible due to the lack of free protons. A new MRI-visible bone cement was developed through the addition of a contrast agent and either a saline solution or a hydroxyapatite (Wichlas et al., 2010). The purposes of the study were to examine the influence of the two MRI-signal-inducing cements on the biomechanical behavior of cadaveric osteoporotic vertebral bodies after vertebroplasty and to compare the performance of the cements with conventional polymethylmethacrylate cement.

Methods

Three different cements were used: standard polymethylmethacrylate cement and two modified MRI-signal-inducing cements that were mixed with either a 0.9% saline solution or a hydroxyapatite. The modulus of elasticity for the standard polymethylmethacrylate cement was 2040 MPa, and the moduli for the MRI-signal-inducing cements that were mixed with a 0.9% saline solution and a hydroxyapatite were 1477 and 1225 MPa, respectively. The lumbar vertebral bodies from nine osteoporotic spines (mean age = 87 years, range = 78–99 years) of female cadavers were examined. Three groups were formed: polymethylmethacrylate cement with saline solution (n = 14), polymethylmethacrylate cement with hydroxyapatite (n = 12) and polymethylmethacrylate cement (n = 13). The vertebral bodies were biomechanically tested before and after vertebroplasty. Stiffness was chosen as the primary biomechanical parameter.

Findings

The vertebral body stiffness was nearly two-fold greater after vertebroplasty, and this increase was statistically significant for every group. All the groups had similar vertebral body stiffness value before and after the vertebroplasty. The UNIANOVA test for multivariate analysis of variance showed no influence of lumbar level, injected cement volume and initial vertebral body stiffness.

Interpretation

The elastic moduli of the cements appear to exert little influence on the biomechanical values when the cement is in the vertebral body. Based on the direct comparison with the classic polymethylmethacrylate cement, we believe that the implementation of such cements for MRI-guided vertebroplasties is feasible.